FIP: Research can explain correlation between high titers, poor prognosis
Q It seems like I have been diagnosing an increasing number of cases of feline infectious peritonitis (FIP). Is the incidence of feline infectious peritonitis on the increase? Are laboratory tests useful?
A Two excellent reviews on the subject of feline infectious peritonitis (FIP) have recently appeared:
- The journal publication of Pollard RE, et al: Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. JAVMA 218:1111-1115, 2001.
- The Web site www.vetscite.org review entitled "An Update on Feline Infectious Peritonitis" authored by Drs. Marian C. Horzinek, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands and Hans Lutz, Department of Internal Veterinary Medicine, University of Zurich, Zurich, Switzerland.
This column will abstract some of the pertinent information about FIP from these two reviews to answer these questions.
Epidemiology of FIP
Evidence suggests FIP virus is the result of a mutation of feline enteric coronavirus (FECV). FIP and FECV are grouped together as feline coronavirus (FCoV) for our current discussion.
According to the results from the mentioned epidemiological study, approximately one of every 200 new feline and one of every 300 total feline accessions at veterinary medical teaching hospitals in North America and approximately one of every 100 accessions at the diagnostic laboratories represented cats with FIP during a 10-year period from January 1986 to December 1995.
The proportion of new accessions for which a diagnosis of FIP was recorded did not vary significantly among years, months or regions of the country. In today's world, cats with FIP are significantly more likely to be young (59 percent from 2 months to 2 years), from pedigree breeding, and be sexually intact males and significantly less likely to be spayed females.
Exposure to FCoV is required for subsequent development of FIP, and the high potential for exposure of cats to FCoV is, in part, responsible for the high proportion of cats with FIP.
The seroprevalence of antibodies to FCoV is estimated to be 25 percent for single-cat households and 75 percent to 90 percent for multiple-cat households.
A diagnosis of FIP can be made in cats with the effusive form of disease based solely on the results of physical examination and fluid evaluation.
Because of the poor prognosis and limited options for long-term therapeutic success, cats with the effusive form of FIP are probably less likely to be referred to a veterinary medical teaching hospital for further evaluation.
On the other hand, diagnosis is more difficult in cats with the dry form of FIP, which represent approximately one of four cats with FIP, and such cats are likely to be referred for further diagnostic testing.
Therefore, the prevalence of FIP among sick cats examined at private veterinary practices may be similar to or greater than that among cats examined at veterinary medical teaching hospitals.
According to international feline researchers,. Horzinek and Lutz, FIP is an important disease to the clinician for several reasons:
- It is fatal in most clinical cases
- Its biology is poorly understood
- Prevention is difficult.
The serologic diagnosis of FIP has been covered in many textbooks and articles. A negative serologic result would not invalidate the diagnosis based on clinical and CBC/serum chemistry profile information.
In the absence of clinical signs, serology is of no use for the prognosis in individual cats. A statistical correlation indeed exists between antibody titers and post-mortem confirmation of FIP three months after testing. However, about 40 percent of the cats with titers of <300 do develop FIP, and of those with titers exceeding 1,000 only about one-half succumb. In other words, about half of the tested cats that remained healthy showed the same high titer values as the cats at risk. Tossing a coin would have given a similar result.
How does the other face of that coin look?
About 12 percent of the cats with titers <100 still developed FIP in the observation period. Based on these data, one in eight owners would have been sent home with the erroneous information that nothing will happen to their cat.
Serology does not distinguish between harmless and FIP-inducing FCoV mutants, it only shows past - and in many cases still ongoing - infection. Any seropositive cat may succumb to FIP, irrespective of the titer.
Prognostic, diagnostic testing
We now can explain this statistical correlation between high titers and poor prognosis.
Expansion of the coronavirus quasispecies cloud obviously not only provides much genomic material with the increased probability for FIP-inducing mutants to occur, it also provides the large antigenic mass to induce high levels of antibody. However, FIP-inducing mutants can always occur, also at low replication levels (with low antibody production), though with a lesser likelihood.
On the other hand, an uninfected cat - which is not synonymous with a seronegative cat - will not develop into a case of FIP. This may sound as a truism, nevertheless some consideration is justified. In a cattery study in Hanover, Germany, a few seronegative kittens shed FCoV in both feces and plasma, some in feces only, and others in plasma only. Eighty-six percent positive animals were detected using polymerase chain reaction (PCR) testing, while serology showed only 71 percent positives. However, not a single seropositive animal tested PCR-negative.
The question must be asked whether there is a place for diagnostic and prognostic laboratory testing for FIP at all.
There are presently no diagnostic assays available - neither in-practice tests nor assays performed in the research laboratory - that would distinguish between virulent FIP virus and avirulent FCoV variants. Also the "novel" PCR formats touted by some companies do not keep this promise, irrespective of their claims. We have reasons to believe that discriminatory assays based on the molecular properties of the variants will not be feasible, perhaps not even possible. However, there is a future for tests based on the evidence of immunological changes in a cat developing FIP.
Both serology and PCR are able to detect infected cats, with different sensitivity, and are invaluable for the management of catteries. They can be used for monitoring the success of the quarantine and early weaning programs, for controlling the specified pathogen-free and the coronavirus-free status of catteries. Especially PCR could be useful for monitoring individual cats to be introduced into FCoV-free catteries.
A promising approach to controlling FIP based on isolation of litters after early weaning has been developed by the research group in Glasgow, Scotland, but it is laborious, requires the dedicated cooperation of cat owners and has no veterinary appeal.
Incidentally, other studies performed under similar conditions showed only marginal effects. Another possibility is the removal of strong shedders from a multiple-cat society. This can now be done by using the TaqMan technique. For a reliable characterization of the shedding pattern it is sufficient to test four feces samples taken at weekly intervals.
Strong shedders can be identified under field conditions and separated from the cat group, thereby decreasing infection pressure for the remaining cats. It remains to be shown whether this approach will work. However, common sense suggests that in conjunction with other measures (keeping cats in small groups, without contact between groups, frequent cleaning of litter boxes, introduction of new cats only after quarantine and PCR testing, etc.) the elimination of strong shedders might be useful.
The seronegative catteries established through any control program must of course be protected against re-introduction of virus, and the live temperature-sensitive FIP vaccine could prove useful for this purpose.